The valves of the heart may be abnormal from birth, may become diseased, or may degenerate in old age. When their function becomes sufficiently impaired they may require to be replaced. There are many different artificial heart valves available for their replacement in established clinical use. In general, these artificial valves have been of two types. Mechanical replacement heart valves are constructed of rigid, synthetic materials such as metallic alloys, pyrolytic carbon, or rigid polymers. They do not resemble natural heart valves. Biological replacement heart valves are constructed of flexible materials of human or animal origin such as human aortic or pulmonary valves, animal aortic or venous valves, or animal pericardium (the fibrous sheet surrounding the heart). Such animal tissues are commonly treated with agents such as glutaraldehyde to enhance their durability. Biological heart valves resemble the natural aortic or pulmonary valves. Glutaraldehyde-treated bovine pericardium is a commonly used material, fashioned into three flexible leaflets on a supporting frame to mimic the natural aortic valve. These valves are implanted into the heart after removal of the abnormal valve by means of an open-heart operation. More recently, flexible valve leaflets have been attached within an expandable mesh-like cylinder for implantation via a catheter introduced into the apex of the heart or via a peripheral blood vessel. After manipulation into the correct location the device is expanded with a balloon to create a functional valve, without the need for conventional invasive surgery.
In general, mechanical valves require life-long anticoagulant drug treatment to prevent blood clotting around the valve and interfering with valve function, or spreading in the bloodstream to block vital arteries to the brain, gut, limbs or other areas, while biological valves are vulnerable to degeneration that limits their useful life, particularly in children and young adults.
Attempts to substitute a synthetic material for the biological material of the valve leaflets have been stimulated by the desire to avoid the leaflet calcification and degeneration, particularly in young adults and children, which detract from the clinical attractiveness of bioprosthetic valves. Most efforts have focussed on biostable polyurethanes. Valve design has resembled that of bioprosthetic valves in the expectation of retaining the low thrombo-embolic risk of these valves.
Synthetic polymeric, flexible-leaflet artificial heart valves, being still at an experimental stage, cannot be said to have a standard, established pattern of design. However, those examples that have been revealed in the literature mimic the design of the standard, established bioprosthetic valve, that in turn resembles the natural aortic valve of the heart. There is a good reason for this as this design retains near natural blood flow through the functioning valve. This is believed to be responsible for the bioprosthetic valve being unlikely to activate the blood clotting mechanisms of the body (“low thrombo-embolic risk”—hence allowing use of these valves without the clinical need for anticoagulation), in contrast to the “unnatural” design and abnormal flow patterns of mechanical valves.
The use of synthetic polymers, such as polyurethane, has been proposed as a possible solution to the limited durability of current flexible-leaflet bioprosthetic heart valves of animal origin. There are few examples of synthetic polymer heart valves in clinical use and these are currently confined to use in extracorporeal circuits where prolonged function is not required. Experimental polymer heart valves have shown limited durability and this is a serious disincentive to further development of such valves for clinical use as valve replacement devices. Experimental polymer heart valves have, in particular, been susceptible to damage such as tearing as a consequence of high localised bending stresses especially caused by buckling or wrinkling that may occur during valve operation.
The available polyurethanes that are suitable for medical use and that are sufficiently biostable for prolonged use in the bloodstream are relatively limited in number and are generally too stiff to allow satisfactory function of leaflets made from polyurethanes. This is particularly apparent with the stiffer, higher modulus, polyurethanes that would have greatest durability and biostability. Furthermore, the use of reinforcement within the polyurethane, such as carbon nanotubes or larger fibres, is likely to increase stiffness and render the reinforced leaflet too stiff for satisfactory haemodynamic function i.e. too stiff to allow the valve to open and close readily with satisfactory pressure drop across the valve and low regurgitation through the valve.
An important group of patients at present have no practical, satisfactory replacement heart valve available to them. This group comprises children and young adults in the developing nations. For example, Sub-Saharan Africa has the largest population of rheumatic heart disease patients in the world (World Health Organisation (WHO) estimates over 1 million aged 5-24 year olds—compared to some 33,000 in the industrialised world). Many of these go on to merit valve replacement. For these young patients the complex valve repair or valve transfer (Ross operation) procedures, sometimes applicable in the developed world, are not a feasible prospect; mechanical valves need life-long anticoagulant therapy (itself needing supervision), with a prohibitive life-long risk of bleeding or valve thrombosis; and biological valves often last only a few years before needing repeat surgery, with its own attendant risks. Thus, for the relatively small number of younger patients in the industrialised world, and for patients who cannot take anticoagulant drugs for medical or life-style reasons there is a pressing need for a durable replacement heart valve that will function clinically satisfactorily without anticoagulant drugs for many years without being vulnerable to early deterioration and failure. However, there is a very much larger population of patients in the developing world who could benefit from such a valve. Access to surgical facilities has often been a limiting factor, but with increasing development in many countries this may well become less of a problem. If a reasonably priced, reliable heart valve that did not require anticoagulation, and was easy to implant in a conventional operating room, were available, there would be a wide clinical application.